Human umbilical cord composition for treatment of peyronie's disease

Abstract

A processed human umbilical cord composition for the treatment of Peyronie's disease by intracorporeal injection in a subject in need thereof with an effective amount of the composition. The composition including an aqueous human umbilical cord filtrate having endogenous hyaluronic acid (HA) and/or hyaluronan, fibronectin, insulin growth factor binding protein-1 (IGFBP-1), sulfated glycosaminoglycans (sGAGs), exosomes, interleukin-1 receptor antagonist (IL-1ra), hepatocyte growth factor (HGF), transthyretin, tissue inhibitor of metalloproteinase 1 (TIMP-1), aggrecan, or a combination thereof therein at effective amount to reduce size of a Peyronie's disease plaque.

What is claimed is: 
     
         1 . An intracorporeal injectable processed human umbilical cord composition for treatment of Peyronie's disease by intracorporeal injection in a subject in need thereof with an effective amount of the composition, the composition comprising:
 (a) an aqueous human umbilical cord filtrate having interleukin-1 receptor antagonist (IL-1ra) present in the aqueous human umbilical cord filtrate at a concentration ranging from 2.0×10 2  pg/mL to 4.0×10 4  pg/mL, tissue inhibitor of metalloproteinase 1 (TIMP-1) present in the aqueous human umbilical cord filtrate at a concentration ranging from 1.0×10 4  pg/mL to 8.0×10 5  pg/mL, insulin growth factor binding protein-1 (IGFBP-1) present in the aqueous human umbilical cord filtrate at a concentration ranging from 1.0×10 4  pg/mL to 6.0×10 6  pg/mL, and at least one of endogenous hyaluronic acid (HA) and/or hyaluronan, fibronectin, sulfated glycosaminoglycans (sGAGs), exosomes, hepatocyte growth factor (HGF), transthyretin, aggrecan, or a combination thereof therein at effective amount to reduce size of a Peyronie's disease plaque.   
     
     
         2 . The composition according to  claim 1 , wherein the aqueous human umbilical cord filtrate has not been subjected to exogenous enzymatic digestion. 
     
     
         3 . The composition according to  claim 1 , wherein the composition does not include particulates exceeding 100 μm in diameter. 
     
     
         4 . The composition according to  claim 3 , wherein the aqueous human umbilical cord filtrate having at least one of acellular Wharton's jelly, hyaluronan (HA) at a concentration ranging from 3.0×10 6  pg/mL to 4.0×10 8  pg/mL, sulfated glycosaminoglycans (sGAGs) at a concentration ranging from 2.0×10 7  pg/mL to 3.0×10 9  pg/mL, transthyretin at a concentration ranging from 1.75×10 2  pg/mL to 6.0×10 5  pg/mL, aggrecan at a concentration ranging from 0 pg/mL to 8.0×10 4  pg/mL or a combination thereof. 
     
     
         5 . The composition according to  claim 4 , wherein the aqueous human umbilical cord filtrate further comprises an isotonic solution. 
     
     
         6 . The composition according to  claim 5 , wherein the isotonic solution is phosphate buffered saline. 
     
     
         7 . The composition according to  claim 6 , wherein the aqueous human umbilical cord filtrate comprises particles from a human umbilical cord tissue that are less than 100 μm in diameter therein. 
     
     
         8 . The composition according to  claim 1 , wherein the aqueous human umbilical cord filtrate is non-immunogenic. 
     
     
         9 . A kit comprising a vial, ampule, or pre-loaded syringe having the processed human umbilical cord composition of  claim 1  therein. 
     
     
         10 . A method for reducing size of a Peyronie's disease plaque in a human subject in need thereof comprising:
 (a) contacting the Peyronie's disease plaque with a predetermined volume of the composition of  claim 1 .   
     
     
         11 . A method of making the composition of  claim 1 , the method comprising:
 (a) providing a human umbilical cord;   (b) washing the human umbilical cord with an isotonic solution;   (c) grinding the washed human umbilical cord of step (b) thereby forming ground human umbilical cord tissue;   (d) separating the ground human umbilical cord tissue of step (c) into a solid retentate and an aqueous human umbilical cord supernatant;
 optionally further processing the solid retentate of step (d) into a micronized human umbilical cord composition; and 
   (e) filtering the aqueous human umbilical cord supernatant thereby forming an aqueous human umbilical cord filtrate, the aqueous human umbilical cord filtrate having particles from the ground human umbilical cord tissue that are less than 100 μm in diameter therein, wherein:
 none of steps (a)-(e) include introduction of exogenous enzymes resulting in exogenous enzymatic degradation/digestion, and 
 before step (d) contacting the ground umbilical cord tissue formed in step (c) with a filter and subsequently filtering the ground umbilical cord tissue to form the solid retentate retained on the filter and the aqueous human umbilical cord supernatant of step (d) that has passed through the filter, and 
 wherein interleukin-1 receptor antagonist (IL-1ra) is present in the aqueous human umbilical cord filtrate at a concentration ranging from 2.0×10 2  pg/mL to 4.0×10 4  pg/mL. 
   
     
     
         12 . The method of  claim 11 , wherein a grinding tool configured to grind and/or mince the washed human umbilical cord is used during step (c) and grinds the washed human umbilical cord at a range of 40 to 200 revolutions per minute (RPM) until the umbilical cord has been fully ground. 
     
     
         13 . The method of  claim 11 , wherein the filter has a porosity ranging from 100 μm to 200 μm. 
     
     
         14 . The method of  claim 13 , wherein the further processing step of the solid retentate is included and is a milling, freeze drying, or dehydration process that forms the micronized human umbilical cord composition having particle sizes ranging from greater than 1 μm to less than 300 μm, with the particles being polydisperse. 
     
     
         15 . The method of  claim 14 , wherein the micronized human umbilical cord composition is a dried micronized human umbilical cord tissue having a particle diameter size ranging from greater than 1 μm to less than 300 μm and comprising collagen, fibronectin, IGFBP-1 at a concentration ranging from 1500 pg/mL to ˜9000 pg/mL, sGAGs at a concentration ranging from 0.1×10 6  pg/ml to 3.0×10 7  pg/mL, exosomes at a concentration ranging from 1.5×10 9  particles/mL to 4.0×10 9  and having a particle size ranging from 50 nm to 200 nm, or any combination thereof. 
     
     
         16 . The method of  claim 15 , wherein the aqueous human umbilical cord filtrate comprises at least one of Wharton's jelly, hyaluronan (HA) at a concentration ranging from 3.0×10 6  pg/mL to 4.0×10 8  pg/mL, sulfated glycosaminoglycans (sGAGs) at a concentration ranging from 2.0×10 7  pg/mL to 3.0×10 9  pg/mL, transthyretin at a concentration ranging from 1.75×10 2  pg/mL to 6.0×10 5  pg/mL, aggrecan at a concentration ranging from 0 pg/mL to 8.0×10 4  pg/mL or a combination thereof. 
     
     
         17 . The method of  claim 11 , wherein both the micronized human umbilical cord composition and the aqueous human umbilical cord filtrate are sterile. 
     
     
         18 . The method of  claim 11 , wherein both the micronized human umbilical cord composition and the aqueous human umbilical cord filtrate are non-immunogenic. 
     
     
         19 . The method of  claim 11 , further comprising:
 tissue inhibitor of metalloproteinase 1 (TIMP-1) at a concentration ranging from 1.0×10 4  pg/mL to 8.0×10 5  pg/mL, and   insulin growth factor binding protein-1 (IGFBP-1) at a concentration ranging from 6.0×10 3  pg/mL to 6.0×10 6  pg/mL.